The invention relates in general to the field of microfluidics and in particular to microfluidic chips equipped with electrodes to perform measurements on liquids in the chip, such as microfluidics for point-of-care diagnostics, as well as related systems and flow monitoring methods.
Microfluidics deals with the behavior, precise control and manipulation of small volumes of fluids that are typically constrained to micrometer-length scale channels and to volumes typically in the sub-milliliter range. Prominent features of microfluidics originate from the peculiar behavior that liquids exhibit at the micrometer length scale. Flow of liquids in microfluidics is typically laminar. Volumes well below one nanoliter can be reached by fabricating structures with lateral dimensions in the micrometer range. Reactions that are limited at large scales (by diffusion of reactants) can be accelerated. Finally, parallel streams of liquids can possibly be accurately and reproducibility controlled, allowing for chemical reactions and gradients to be made at liquid/liquid and liquid/solid interfaces.
More in detail, typical volumes of fluids in microfluidics range from 10−15 L to 10−4 L and are transported, circulated or more generally moved via channels (or microchannels) having a typical diameter of 10−7 m to 10−4 m. At the microscale, the behavior of fluids can differ from that at a larger, e.g., macroscopic, scale, such that surface tension, viscous energy dissipation and fluidic resistance may become dominant characteristics of the fluid flow. For instance, in microfluidics, the Reynolds number, which compares the effects of fluid momentum and viscosity, may decrease to such an extent that the flow behavior becomes laminar rather than turbulent.
In addition, at the microscale, fluids do not necessarily chaotically mix as at the microscale due to absence of turbulence in low Reynolds number flows, and interfacial transport of molecules or small particles between adjacent fluids often takes place through diffusion. As a consequence, certain chemical and physical fluid properties (such as concentration, pH, temperature and shear force) may become deterministic. This makes it possible to obtain more uniform chemical reaction conditions and higher-grade products in single and multi-step reactions.
Microfluidic devices generally refer to microfabricated devices, which are used for pumping, sampling, mixing, analyzing and dosing liquids. The majority of microfluidic devices are sealed and have inlets/outlets for pumping in and out liquids through them. Some microfluidic devices such as the so-called “microfluidic probes”, however, can scan surfaces and localize liquids on selected areas of surfaces without the need for sealing the flow paths.
Microfluidic devices for point-of-care diagnostics are devices meant to be used by non-technical staff, near patients or in the field, and potentially at home. Existing point-of-care devices typically require loading a sample onto the device and waiting a predefined time until a signal (usually optical or fluorescence signal) can be read. The signal originates from (bio)chemical reactions and relates to the concentration of an analyte in a sample. These reactions take times and are difficult to implement because they require optimal timing, flow conditions of sample and accurate dissolution of reagents in the device. The reactions involve fragile reagents such as antibodies. Air bubbles may be created in the device, which can invalid tests. In addition, debris in a device can block liquid flows. In devices where liquids must be split in parallel flow paths, filling may not occur at the same flow rate and this can bias or invalidate the tests. In addition, some tests fail due to manufacturing problems.
Moreover, microfluidic devices for point-of-care diagnostics are typically non-transparent (to protect reagents from light) and are usually too small to allow optical flow monitoring, which would require bulky and expensive optical systems and/or advanced image processing algorithms
Instead of using active pumping means, microfluidic devices are known, which use capillary forces for moving a liquid sample inside the microfluidic device. This makes the device simpler to operate and less expensive because there is no need for integrated or external pump. However, particulates, contamination and other issues during manufacture can compromise capillary-based filling of the device.